Although high levels of polyamines, viz., putrescine, spermidine and spermine, are associated with rapid growth and cell division in eukaryotic systems, relatively little is known about their role in growth regulation. The recent discovery of specific inhibitors of polyamine biosynthesis, such as methyl gloxal bis (guanylhydrazone), alpha-methyl ornithine, and 1,3-diaminopropane has opened up a new chapter in understanding the relationship between polyamine levels and other cellular functions. It is now well established that polyamines are essential for DNA synthesis in mammalian cells. Our preliminary studies with methyl glyoxal bis (guanylhydrazone) on HeLa and Chinese hamster ovary cells revealed that depletion of spermidine and spermine levels affect not only DNA synthesis but also chromosome condensation, cytokinesis, regulation of nuclear division and in vitro differentiation of mouse neuroblastoma cells. Under this project we propose to pursue these leads in a detailed and systematic fashion using the techniques of cell fusion, premature chromosome condensation, scanning and transmission electron microscopy for ultrastructural studies of prematurely condensed chromosomes and immunoelectron-microscopy to determine the role of polyamines in the structure and function of micro-filaments. We also propose to study the molecular basis for the relationship between the depletion of polyamines and the inhibition of DNA synthesis. The role of polyamines in the regulation of nuclear division in normal and transformed cells will also be studied. The results of these studies may provide some clues as to how we could interrupt the division cycle of tumor cells by disrupting the biosynthesis of specific polyamines. A better understanding of the roles of polyamines at various points in the mammalian cell cycle may prove to be helpful in the control or treatment of human malignancies.